In the event of a radiological or nuclear incident in a large US city, tens or hundreds of thousands of individuals would require rapid dosimetric screening. Mass radiological triage is critical after such a large-scale event because of the need to identify, at an early stage, those individuals who will benefit from medical intervention, and those who will not. Identifying those patients who do not require treatment, the “worried well,” will also be crucial in what will certainly be a highly resource-limited scenario. The ability to offer prompt reassurance to the majority of the affected population may also assist in stemming the spread of fear and panic. Identification not only of exposure, but also of dose ranges will also be critical, as the appropriate treatment varies depending on dose. The use of antibiotics, platelet and cytokine treatment (Anno, Young, et al., 2003) can significantly increase survival in the range of 1.5 to 7 Gy, while bone marrow transplantation is most useful between 7 and 10 Gy. At doses above 10 Gy, patients will generally suffer lethal gastrointestinal damage (Hall, 2000). Physical dosimetry will not be readily available for individuals in the general population.
The range of potential biodosimeters have been reviewed by several groups (see e.g., Amundson, Bittner, Trent, Fornace) (16). The following table, adapted from Amundson et al. (16), gives a brief summary of currently possible biodosimeters.
Post-HighBaselineDetectionRadiationexposurethroughputAssayEase of assayvariabilitylimit (Gy)specificitylongevitypotential?ESR/EPRDifficultHigh0.1GoodyearsNoBlood countsSimple, butLow1GoodweeksNomultiple repeatsrequiredSomaticMutationgpa by flowSimpleModerate1-2Good, but only foryearsYescytometry½ of populationhprt-T-cellSimpleModerate1-2ModeratemonthsNocloningCytogeneticsDicentrics/ModerateModerate0.3Goodyears forNotranslocationstranslocationsMicronucleiSimpleModerate0.3GoodmonthsYesPCCSimpleModerate0.3GooddaysYesDSB (γ-H2AX)SimpleModerate0.3GooddaysYesGenomicsMultiplex PCRPotential toLow?0.2Low-ModeratedaysYessimplifyGene ProfilesPotential toLow?0.2Good?daysYessimplifyMetabolomicsProfilingPotential to beLow???days?Yesvery simple
Early studies using gene expression to classify sample groups have demonstrated the need for sets of multiple biomarkers to attain accurate classification and resistance to noise, with even relatively homogeneous groups requiring from 10 to 200 genes for correct classification (26-28). Work has been done that assesses radiation-induced gene expression signatures, both in vitro (29-35) and in vivo (36), and also suggests that gene expression assays involving a very small number of genes would not be able to accurately assess radiation dose or distinguish radiation exposure from other generalized stress responses. This would rule out, for example, quantitative reverse transcription PCR (QRT-PCR), which, though clearly amenable to automation (37), can realistically only measure the expression of three different genes simultaneously, which would be inadequate for the required radiation specificity.
Thus, there exists a critical need for the development and validation of methods and devices to exploit the biological responses to radiation exposure as a means of obtaining the needed dosimetric information.